This application relates to the in vivo antimicrobial use of electrically hydrolyzed salines. More particularly, this invention relates to the treatment of antigen related infections in warm blooded animals by the intravenous injection of electrically hydrolyzed saline solutions which mimic or enhance the naturally occurring chemicals produced in vivo by the body in responding to such infections.
Phagocytic cells (neutrophils, monocytes, eosinophils, macrophages, and large granular lymphocytes, collectively called "killer cells") give off superoxide in what is called the "respiratory burst" which has an antimicrobial action and, if not properly controlled, can also cause tissue damage. The superoxide radical itself may not be directly responsible for the microbicidal action. Rather, this activity and any resultant tissue damage may be attributed to superoxide derivatives such as hydrogen peroxide, hydroxyl radical and possibly, singlet oxygen. Polymorphonuclear neutrophils and macrophages not only give off superoxide, leading to the production of hydrogen peroxide and hydroxyl free radical , but also generate hypohalous acids and N-chloroamines as one of their mechanisms which also destroy bacteria. These leukocytes consume oxygen which is transformed by membranous reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to superoxide.
The "respiratory burst" is observed as a dramatic increase in the consumption of oxygen and the activation of a membrane-associated NADPH oxidase. This oxidase reduces molecular oxygen to superoxide anions, which in turn dismutates to hydrogen peroxide. Superoxide and hydrogen peroxide can interact to give rise to the hydroxyl radical and possibly also to singlet oxygen. The superoxide anion, hydrogen peroxide, hydroxide radicals and singlet oxygen, all possess antimicrobial activity and are quite unstable. The respiratory burst continues during phagocytosis by polymorphonuclear leukocytes until engulfment is complete. The respiratory burst may also occur in leukocytes under various chemical influences in addition to phagocytosis.
The respiratory burst, although intimately connected with phagocytosis, is not an essential accompaniment to phagocytosis. Recent evidence suggests that free tissue macrophages and newly recruited monocytes, as distinguished from fixed tissue macrophages, can respond to lymphokines and phagocytic stimuli by mounting a respiratory burst. The failure of fixed tissue macrophages, such as Kupffer cells, to produce active metabolites of oxygen may be important in protecting tissues from damage during the scavenger functions of the macrophage. Many soluble agents, including antigen/antibody complexes, C5a, ionophores and tumor promoters, can trigger the respiratory burst without phagocytosis. The respiratory burst can also be triggered by opsonized particles or surfaces when phagocytosis is frustrated by the use of a drug such as cytochaiasin B. In addition to the reactive species of oxygen referred to above, i.e. superoxide anions, hydrogen peroxide, hydroxyl radicals, and singlet oxygen, there are a number of other potential microbicidal mechanisms in macrophages many of which are oxygen dependent. A major oxygen dependent system is mediated by myeloperoxidase (MPO) , which catalyzes oxidation of a number of substances to hydrogen peroxide. MPO is the oxidase of neutrophils and the green color of pus is due to its presence. A cofactor in the MPO system is the iodide ion from the thyroid hormones, thyroxine or triiodothyronine. However, this microbicidal system sometimes also utilizes other halide ions such as bromide or chloride as cofactors in the place of iodide.
It is well documented that two free radicals of superoxide combine with hydrogen to form normal oxygen and hydrogen peroxide. This is known as the dismutation reaction with superoxide dismutase (SOD) acting as the catalyst. Unless hydrogen peroxide is denatured promptly with catalases or peroxidases, there is an interaction between superoxide and hydrogen peroxide leading to the production of the highly reactive hydroxyl radicals via pathways known as the Haber-Weiss or Fenton's reactions. Singlet oxygen is also generated by the removal of the unpaired electrons of the superoxide radical.
Leukocytes, in vivo, use the formation of superoxide, hydrogen peroxide, hydroxide radicals, singlet oxygen and halogenated products such as hypochlorous acid to destroy bacteria, fungi and viruses and perhaps also tumor cells. Other oxygen-dependent antimicrobial systems , unrelated to MPO, are also believed to rely on the production of hydrogen peroxide, superoxide anion, the hydroxyl radical and/or singlet oxygen to do the microbial killing in vivo. Some of these systems are not well documented but it is known that when such systems shut down or operate inefficiently, severe infections results.
There are also problems involved with over production or an excess of these radicals within the cells of the host. Hence, the body has provided means for mediating or neutralizing these products once they have performed their antimicrobial functions.
As previously mentioned SOD is effective in scavenging superoxide radicals (each containing an unpaired electron) in a simultaneous oxidation-reduction reaction with hydrogen called dismutation. Two superoxide radicals combine with two hydrogen atoms to form hydrogen peroxide and oxygen. Hydrogen peroxide is reduced by the enzymes catalase, glutathione peroxidase and MPO into oxygen and water.
Hence, in a normal functioning host, such as in a human or other warm blooded animal, there is an intra vivo interaction and balance maintained between respiratory bursts brought on by the presence of an invading foreign substance such as bacteria, virus or fungi accompanied by the formation of superoxide, hydrogen peroxide, hydroxyl radicals, singlet oxygen, hypohalous acids, and hypochlorite ions [collectively referred to as free radicals ] with their accompanying antimicrobial actions and the mediating or neutralizing action of the enzymes SOD, MPO, glutathione, glutathione peroxidase, catalase, ascorbic acid and its salts and perhaps others.
There are situations when there is not sufficient free radicals present to accomplish their desired tasks. There are numerous bacterial, viral, fungal related syndromes and immunological disorders wherein it would be beneficial to have free radicals available to the cells for the short period required for their antimicrobial action followed by mediation and/or neutralization of the free radicals. Examples of such syndromes and/or immunological disorders are multiple sclerosis, cardiomyopathy (viral myocarditis), viral associated autoimmune diseases and perhaps even AIDS related syndromes . These are all diseases which are affected by slow, latent or temperate virus which have long incubation periods and, in some cases, have a low ratio of reported cases to infections. They are also diseases for which there is no known cure and usually slowly progress until they, or a concurrent opportunistic infection, results in the death of the host.
An infected host or patient may be treated by a variety of regimens which may alleviate the symptoms for a time. However, the immune system eventually is weakened to the point that it can no longer adequately contend with the invading or autoimmune related infections and the natural biocidal action in the cells ceases to function properly.